POS0712 YEAR-4 OBSERVATIONAL FOLLOW-UP OF BELIMUMAB SAFETY (MORTALITY AND MALIGNANCIES) IN PATIENTS WITH SLE WHO COMPLETED A PHASE 4, 52-WEEK, RANDOMISED, DOUBLE-BLIND PLACEBO-CONTROLLED SAFETY STUDY
Authors: S. Sheikh, M. Scheinberg, J. C. C. Wei, D. Tegzová, W. Stohl, R. Acayaba De Toledo, T. Mucenic, M. R. Abello Banfi, K. Maksimowicz-Mckinnon, C. Abud-Mendoza, S. Navarra, M. García, I. Garcia-De La Torre, A. Liu, A. Roy, P. Wilde, S. Fernandes, J. Harris, D. Roth
Journal: Annals of the Rheumatic Diseases (2022)

Background Belimumab (BEL) is an approved systemic lupus erythematosus (SLE) treatment. Despite BEL clinical studies demonstrating a favourable benefit–risk profile, varying incidence rates of mortality and adverse events of special interest, including malignancies, require further evaluation. Objectives To assess long-term safety following BEL therapy. Methods This was a Year (Yr)-4 post-treatment follow-up of the Phase 4, double-blind, placebo (PBO)-controlled Belimumab Assessment of Safety in SLE (BASE) study (GSK Study BEL115467; NCT01705977 ). 1 Overall, 4003 adults with active, autoantibody-positive SLE received BEL (10 mg/kg IV) or PBO, plus standard therapy (ST), for 48 weeks. Patients (pts) then entered a Yr 2–5 follow-up period in which they received physician-directed ST. All pts were contacted annually by telephone, including pts who discontinued treatment. Mortality and new malignancies (including nonmelanoma skin cancer) were the endpoints collected, and rates summarised. We present Yr-4 follow-up data by Yr-1 treatment received. Results Baseline characteristics for the Yr-4 follow-up population (N=3204) were similar to the Yr-1 double-blind study population (N=4003). By the Yr-4 follow-up, cumulatively 12.7% and 11.0% of pts in the BEL and PBO Yr-1 groups had received BEL as part of physician-directed care, respectively (data not shown). As shown in the Table 1, cumulative follow-up adjusted mortality rates were lower in the BEL vs PBO Yr-1 treatment group for Yrs 2 to 4. Cumulative follow-up adjusted new primary malignancy rates were lower in the BEL vs PBO Yr-1 treatment group for Yrs 2 and 3, but similar in Yr 4. Table 1. Yr 1 plus Yrs 2–4 post-treatment* follow-up mortality and new primary malignancy rates by Yr-1 study treatment Pts with events per yr, n (%) Pt incidence rate per 100 pt-yrs (Cumulative rate, %) BEL PBO Total BEL PBO Total Yr-1 (as-treated) population N=2002 N=2001 N=4003 Deaths 13 (0.65) 22 (1.10) 35 (0.87) 0.66 (0.65) 1.11 (1.10) 0.87 New primary malignancies† 9 (0.45) 10 (0.50) 19 (0.47) 0.45 0.50 0.47 Yr-2 (as-treated in Yr-1) population N=1695 N=1670 N=3365 Deaths 9 (0.53) 21 (1.26) 30 (0.89) 0.60 (1.10) 1.18 (2.15) 0.89 (1.62) New primary malignancies 3 (0.18) 7 (0.42) 10 (0.30) 0.34 (0.60) 0.48 (0.85) 0.41 (0.72) Yr-3 (as-treated in Yr-1) population N=1659 N=1630 N=3289 Deaths 9 (0.54) 17 (1.04) 26 (0.79) 0.58 (1.55) 1.14 (3.00) 0.86 (2.27) New primary malignancies, n (%) 7 (0.42) 9 (0.55) 16 (0.49) 0.37 (0.95) 0.49 (1.25) 0.43 (1.10) Yr-4 (as-treated in Yr-1) population N=1622 N=1582 N=3204 Deaths by MedDRA SOC 14 (0.86) 13 (0.82) 27 (0.84) 0.65 (2.25) 1.07 (3.65) 0.86 (2.95) Infections/infestations 4 (0.25) 5 (0.32) 9 (0.28) Cardiac disorders 2 (0.12) 1 (0.06) 3 (0.09) General disorders/ administration site conditions 2 (0.12) 2 (0.13) 4 (0.12) Respiratory/thoracic/ mediastinal disorders 2 (0.12) 1 (0.06) 3 (0.09) Nervous system disorders 2 (0.12) 1 (0.06) 3 (0.09) Other‡ 2 (0.12) 3 (0.18) 5 (0.15) New primary malignancies 10 (0.62) 5 (0.32) 15 (0.47) 0.43 (1.45) 0.44 (1.45) 0.43 (1.45) *Pts in the post-treatment follow-up period are no longer receiving study treatment. †Includes nonmelanoma skin cancer. ‡Contains 1 event for 5 distinct pts of each of renal/urinary disorders, and neoplasms (BEL); musculoskeletal/connective tissue disorders, injury/poisoning/procedural complications, and vascular disorders (PBO). MedDRA, Medical Dictionary for Regulatory Activities; SOC, system organ class Conclusion Post-treatment Yr-4 follow-up results in BASE, the largest double-blind trial in pts with SLE to date, support the safety of BEL therapy, with no new BEL safety concerns identified in this analysis. References [1]Sheikh SZ, et al . Lancet Rheumatol 2020;3:e122–30 Acknowledgements This analysis was funded by GlaxoSmithKline (GSK). Medical writing support was provided by Lulu Hill, MPharmacol, Fishawack Indicia Ltd. UK, part of Fishawack Health, and was funded by GSK. Disclosure of Interests Saira Sheikh Consultant of: GSK, Grant/research support from: Pfizer, Morton Scheinberg Consultant of: GSK, Pfizer, Alnylam, AbbVie, PTC Therapeutics, James Cheng-Chung Wei Consultant of: TSH Biopharm, AbbVie, BMS, Celgene, Chugai, Eisai, Janssen, Novartis, Pfizer, Sanofi-Aventis, and UCB Pharma, Grant/research support from: AbbVie, Amgen, Astellas, BMS, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sun and UCB Pharma, Dana Tegzová: None declared, William Stohl Consultant of: GSK, Grant/research support from: GSK, Pfizer, Gilead, RICARDO ACAYABA DE TOLEDO Speakers bureau: AbbVie, Janssen, UCB, Novartis, Celltrion, Consultant of: AbbVie, Janssen, Novartis, UCB, Grant/research support from: Pfizer, AbbVie, Novartis, GSK, Tamara Mucenic Speakers bureau: Novartis, Janssen, BMS, AbbVie, Pfizer, Roche, Grant/research support from: GSK, Janssen, Roche, Eli Lilly, Gilead, UCB, Mauricio R Abello Banfi: None declared, Kathleen Maksimowicz-McKinnon Grant/research support from: Chemocentryx, Carlos Abud-Mendoza Speakers bureau: GSK, Lilly, Pfizer, Sandra Navarra Speakers bureau: Pfizer, Novartis, Johnson &amp; Johnson, Consultant of: Biogen, Boehringer Ingelheim, Grant/research support from: Astellas, Mercedes García Speakers bureau: GSK, Janssen, Pfizer, Ignacio Garcia-De La Torre: None declared, Andrew Liu Shareholder of: GSK, Employee of: GSK, Abhishek Roy Employee of: GSK, Paul Wilde Shareholder of: GSK, Employee of: GSK, Sofia Fernandes Shareholder of: GSK, Employee of: GSK, Julia Harris Shareholder of: GSK, Employee of: GSK, David Roth Shareholder of: GSK, Employee of: GSK